Synthesis of Novel Symmetrical and Unsymmetrical o-Phthalic Acid Diamides

Phthalic anhydride was treated with secondary amines in acetic acid yielding 2-(diethyl (or) 4-alkylpiperazine or morpholine-1-carbonyl) benzoic acids. The latter were reacted, again, with secondary amines and arylamines by using the coupling reagent HATU and Et3N as a base in DMF giving the novel symmetrical o-phthalic acid diamides , unsymmetrical o-phthalic acid diamides , and primary amidic-secondary amidic containing unsymmetrical o-phthalic acid diamides , respectively. 1. Introduction Phthalic anhydride is used in the manufacture of dialkylphthalates [1, 2] which find application as plasticisers for polymers like polyvinyl chloride (PVC) and polyvinylacetate (PVA). It is used in the manufacture of phenolphthalein indicator [3, 4], anthraquinone [5] (a versatile, raw materials in the dye industry [6]), and metal phthalocyanines [7]. Phthalocyanine compounds are used in a variety of applications [7] in addition to their use as pigments, in paints [8] and in many types of dyestuffs [7]. Phthalic anhydride derivatives have been widely reported to possess beneficial pharmaceutical effects, like analgesic [9], anti-inflammatory [10] and antiviral effects [11]. Dunlap and Cummer reported [12] the preparation of symmetrical o-phthalic acid diamides [o-ArNHCOC6H4CONHAr] by the reaction of phthaloyl dichloride with two moles of aniline in ether at RT. Dann et al. reported [13] the preparation of symmetrical o-phthalic acid diamides by the reaction of phthaloyl dichloride with two moles of aniline in the presence of sodium fluoride in benzene under reflux for 1？h. de Toranzo and Brieux reported [14] the synthesis of unsymmetrical diamides [ArNHCOC6H4CONHAr1] by the reaction of phthalphenylisoimide with anilines in ether at RT. Reynolds reported [15] that unsymmetrical diamides [ArNHCOC6H4CONHAr1] can be made by the reaction of N-arylphthalamic acid with the sodium salt of o- or p-methylaniline in an atmosphere of nitrogen for 1？h at 75°C. However, these methods suffer from drawbacks such as long reaction times, excess use of organic solvents, harsh refluxing conditions, and preparation of difficult starting materials from phthalic anhydride by the reaction with primary amines in the presence of trifluoroacetic anhydride. Keeping these facts in mind, we wish to report our results on reactions of phthalic anhydride with primary and secondary amines using HATU as a coupling reagent. Probably, this appears to be the first ever case of facile preparation of symmetrical and unsymmetrical o-phthalic acid diamides. The use of HATU as a coupling agent has been